Journal articles on the topic 'Lipid metabolism; Ketone body metabolism; Carnitine'
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Singer, Thomas D., Vhundi G. Mahadevappa, and James S. Ballantyne. "Aspects of the Energy Metabolism of Lake Sturgeon,Acipenser fulvescens, with Special Emphasis on Lipid and Ketone Body Metabolism." Canadian Journal of Fisheries and Aquatic Sciences 47, no. 5 (May 1, 1990): 873–81. http://dx.doi.org/10.1139/f90-100.
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Key enzymes in several metabolic pathways in five tissues were measured in a primitive osteichthyan, the lake sturgeon (Acipenser fulvescens). Levels of nonesterified fatty acids (NEFAs) were measured in the plasma as an indicator of fatty acid mobilization and differential utilization of individual NEFAs as substrates for lipid oxidation. The metabolism of lake sturgeon differs from that of most teleosts studied; it has detectable levels of beta-hydroxy-butyrate dehydrogenase in all tissues, possibly a primitive metabolic feature of vertebrates, subsequently lost in the teleosts. Based on HOAD and CPT activities lipid oxidation in extrahepatic tissues of sturgeon is intermediate between elasmobranch and teleost models. Sturgeon plasma NEFA concentrations are clearly higher than those detected in any elasmobranch, indicating that the acipenserid chondrosteans may be among the first jawed fish to mobilize and transport NEFAs. Oleic acid (18:1,n9) which amounts to 45% of total NEFA content of the plasma may be a preferred substrate of carnitine dependent oxidation. High levels of long chain fatty acid in the plasma may represent a high turnover of eicosanoid precursors. The low levels of LDH in the anoxia tolerant sturgeon may indicate that alternative anaerobic end products, perhaps ethanol, are used to survive under anoxic conditions.
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Singer, Thomas D., and James S. Ballantyne. "Metabolic Organization of a Primitive Fish, the Bowfin (Amia calva)." Canadian Journal of Fisheries and Aquatic Sciences 48, no. 4 (April 1, 1991): 611–18. http://dx.doi.org/10.1139/f91-078.
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Key enzymes in several metabolic pathways in five tissues were measured in primitive osteichthyan, the bowfin (Amia calva), the only living representative of the group of extant fishes most closely allied to the teleosts. Aspects of the metabolism of Amia differ from those of most teleosts studied. These differences include detectable levels of β-hydroxybutyrate dehydrogenase in all tissues, possibly a primitive metabolic feature of vertebrates, subsequently lost in most more advanced teleosts. Based on 3-hydroxyacyl CoA dehydrogenase and carnitine palmitoyltransferase activities, lipid metabolism in extrahepatic tissues of bowfin more closely resembles that of an elasmobranch rather than that of a teleost. The overall level of metabolism is lower than most teleosts as indicated by enzyme activities in red muscle and heart. Bowfin plasma nonesterified fatty acid concentrations are lower than most teleosts, but higher than those detected in any elasmobranch. These data suggest that the metabolic organization, especially lipid and ketone body metabolism, at least in part, reflects the evolutionary history of this group.
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ZORZANO, Antonio, César FANDOS, and Manuel PALACÍN. "Role of plasma membrane transporters in muscle metabolism." Biochemical Journal 349, no. 3 (July 25, 2000): 667–88. http://dx.doi.org/10.1042/bj3490667.
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Muscle plays a major role in metabolism. Thus it is a major glucose-utilizing tissue in the absorptive state, and changes in muscle insulin-stimulated glucose uptake alter whole-body glucose disposal. In some conditions, muscle preferentially uses lipid substrates, such as fatty acids or ketone bodies. Furthermore, muscle is the main reservoir of amino acids and protein. The activity of many different plasma membrane transporters, such as glucose carriers and transporters of carnitine, creatine and amino acids, play a crucial role in muscle metabolism by catalysing the influx or the efflux of substrates across the cell surface. In some cases, the membrane transport process is subjected to intense regulatory control and may become a potential pharmacological target, as is the case with the glucose transporter GLUT4. The goal of this review is the molecular characterization of muscle membrane transporter proteins, as well as the analysis of their possible regulatory role.
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Ballantyne, J. S., D. Flannigan, and T. B. White. "Effects of Temperature on the Oxidation of Fatty Acids, Acyl Carnitines, and Ketone Bodies by Mitochondria Isolated from the Liver of the Lake Charr, Salvelinus namaycush." Canadian Journal of Fisheries and Aquatic Sciences 46, no. 6 (June 1, 1989): 950–54. http://dx.doi.org/10.1139/f89-122.
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Mitochondria isolated from the liver of the Lake Charr Salvelinus namaycush oxidize a wide range of acyl chain lengths of fatty acids and acyl carnitines at 1, 10, and 20 °C. For most carbon chain lengths the relative importance of carnitine-dependent fatty acid oxidation increases with increasing temperature due to greater thermal enhancement of carnitine-dependent oxidation. At low temperatures the rate of carnitine-independent fatty acid oxidation rivals that of carnitine-dependent oxidation. Therefore, acute temperature shifts during excursions above the thermocline would have important effects on the oxidation of dietary and depot lipids. Temperature does not substantially affect the chain length preference for fatty acid oxidation either in the presence or absence of carnitine, suggesting acclimation-induced changes in substrate specificity of fatty acid oxidation may not be necessary. The importance of β-hydroxybutyrate as an oxidative substrate increases at low temperatures relative to other substrates while acetoacetate oxidation is greater than that of β-hydroxybutyrate at 10 and 20 °C. Altered ketone body metabolism may play a role in regulating cholesterol levels to alter membrane fluidity.
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Miki, C., A. D. Mayer, J. A. C. Buckels, K. Iriyama, H. Suzuki, and P. McMaster. "Serum hepatocyte growth factor as an index of extensive catabolism of patients awaiting liver transplantation." Gut 44, no. 6 (June 1, 1999): 862–66. http://dx.doi.org/10.1136/gut.44.6.862.
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BACKGROUNDWhole body catabolism as the result of intrahepatic metabolic derangement is common in liver transplant candidates. However, individual nutritional assessment parameters lack sensitivity and specificity in determining energy status of these patients. Recently, serum hepatocyte growth factor (HGF) has been shown to reflect the recovery of hepatic energy metabolism after liver transplantation.AIMSThe relation between preoperative levels of serum HGF and metabolic variables was investigated to clarify the clinical value of measuring HGF in evaluations of the catabolism.PATIENTS/METHODSBlood samples were obtained from 30 liver transplant recipients, and biopsy specimens were taken from each recipient’s rectus muscle and the explanted liver. Preoperative serum concentration of HGF was determined. Whole body energy metabolism was assessed by measuring glycogen contents of biopsy specimens and plasma or serum levels of glucose, insulin, total ketone bodies, total carnitine, and amino acids.RESULTSSerum HGF concentration was elevated in 22 of 30 patients and correlated with the Child-Pugh score. It showed a negative association with muscle glycogen content, and a positive correlation with serum levels of glucose, total carnitine, and total ketone bodies. Patients with elevated serum HGF concentrations had higher preoperative plasma levels of aromatic amino acids and branched chain amino acids, associated with lower branched chain to aromatic amino acid ratios.CONCLUSIONSThe elevated serum concentration of HGF in liver transplant candidates reflected inhibition of peripheral glucose storage, enhanced lipid oxidation, and increased peripheral release of branched chain amino acids, and thus extensive energy catabolism.
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Lytle, Kelli A., Nikki C. Bush, Jessica M. Triay, Todd A. Kellogg, Michael L. Kendrick, James M. Swain, Nicola W. Gathaiya, Kazanna C. Hames, and Michael D. Jensen. "Hepatic Fatty Acid Balance and Hepatic Fat Content in Humans With Severe Obesity." Journal of Clinical Endocrinology & Metabolism 104, no. 12 (August 13, 2019): 6171–81. http://dx.doi.org/10.1210/jc.2019-00875.
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Abstract Objective Nonalcoholic fatty liver disease can lead to hepatic inflammation/damage. Understanding the physiological mechanisms that contribute to excess hepatic lipid accumulation may help identify effective treatments. Design We recruited 25 nondiabetic patients with severe obesity scheduled for bariatric surgery. To evaluate liver export of triglyceride fatty acids, we measured very-low-density lipoprotein (VLDL)–triglyceride secretion rates the day prior to surgery using an infusion of autologous [1-14C]triolein-labeled VLDL particles. Ketone body response to fasting and intrahepatic long-chain acylcarnitine concentrations were used as indices of hepatic fatty acid oxidation. We measured intraoperative hepatic uptake rates of plasma free fatty acids using a continuous infusion of [U-13C]palmitate, combined with a bolus dose of [9,10-3H]palmitate and carefully timed liver biopsies. Total intrahepatic lipids were measured in liver biopsy samples to determine fatty liver status. The hepatic concentrations and enrichment from [U-13C]palmitate in diacylglycerols, sphingolipids, and acyl-carnitines were measured using liquid chromatography/tandem mass spectrometry. Results Among study participants with fatty liver disease, intrahepatic lipid was negatively correlated with VLDL-triglyceride secretion rates (r = −0.92, P = 0.01) but unrelated to hepatic free fatty acid uptake or indices of hepatic fatty acid oxidation. VLDL-triglyceride secretion rates were positively correlated with hepatic concentrations of saturated diacylglycerol (r = 0.46, P = 0.02) and sphingosine-1-phosphate (r = 0.44, P = 0.03). Conclusion We conclude that in nondiabetic humans with severe obesity, excess intrahepatic lipid is associated with limited export of triglyceride in VLDL particles rather than increased uptake of systemic free fatty acids.
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Li, Shangbiao, Xiaoxia Zhu, Lijuan Wang, and Zhihao Zheng. "The role of radiation dose-dependent enhancement of fatty acid oxidation in radiation surviving/resistant lung cancer cells." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): e21724-e21724. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e21724.
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e21724 Background: Radiotherapy plays a critical role in the integrated management of lung cancer. However, radioresistance limits the long-term control. Exploring the dynamic changes of metabolic reprogramming in radiation surviving/resistant (S/R) lung cancer cells is helpful to clarify the metabolic mechanism of radiation resistance and to develop new targets for intervention and early detection. Methods: Cell lines were irradiated with different doses (2Gy × 20F, 2Gy × 30F, 2Gy × 40F) in conventional dose fractionation. The cellular radiosensitivity was verified by colony formation assay and neutral comet assay. Cell proliferation ability was determined by EdU assay. Metabonomic analysis was used to identify the differentially expressed metabolites between high-dose radiation-resistant cells and their parent cells. Lipid droplet content was detected by Oil Red O (ORO) staining. Cell oxygen consumption rate (OCR) was measured by Seahorse XF24e analyzer. Western blot was used to detect the expression of metabolic enzymes. The growth of xenograft tumors from these cell lines in BALB/c nude mice were measured after the treatment of radiation (2Gy×5F), Etomoxir, or radiation combined with Etomoxir. Results: Compared with parent cells, the radioresitance of S/R lung cancer cells after different doses of radiationwas significantly increased with the increase of radiation exposure. ORO staining showed that fatty deposition of radiation S/R cells was obviously higher than their parent cells, and more fatty deposition in cells received higher dose of radiation. The ketone body metabolism-related substances, including acetoacetic acid, a metabolite of FAO, were significantly enriched in high-dose radiation-resistant cells. The expression of carnitine palmitoyltransferase1 (CPT1) and the OCR in radiation S/R cells were also radiation-dose dependently increased. Etomoxir, an inhibitor of fatty acid oxidation, significantly enhanced the radiosensitivity and decreased the OCR and DNA repair ability of various S/R cells exposed to radiation. We further confirmed that Etomoxir could significantly inhibit proliferation of radiation S/R cells in vivo, which also presented with radiation-dose dependent model. Conclusions: The enhancement of radiation dose-dependent FAO promotes radiation surviving/resistance of lung cancer cells. CPT1A, a key metabolic enzyme mediating FAO, may be a potential target for treatment of radiation resistant lung cancer. Funding: 81972853, 81572279, 2016J004, LC2019ZD009, 2018CR033.
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Miyamoto, Junki, Ryuji Ohue-Kitano, Hiromi Mukouyama, Akari Nishida, Keita Watanabe, Miki Igarashi, Junichiro Irie, et al. "Ketone body receptor GPR43 regulates lipid metabolism under ketogenic conditions." Proceedings of the National Academy of Sciences 116, no. 47 (November 4, 2019): 23813–21. http://dx.doi.org/10.1073/pnas.1912573116.
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Ketone bodies, including β-hydroxybutyrate and acetoacetate, are important alternative energy sources during energy shortage. β-Hydroxybutyrate also acts as a signaling molecule via specific G protein-coupled receptors (GPCRs); however, the specific associated GPCRs and physiological functions of acetoacetate remain unknown. Here we identified acetoacetate as an endogenous agonist for short-chain fatty acid (SCFA) receptor GPR43 by ligand screening in a heterologous expression system. Under ketogenic conditions, such as starvation and low-carbohydrate diets, plasma acetoacetate levels increased markedly, whereas plasma and cecal SCFA levels decreased dramatically, along with an altered gut microbiota composition. In addition, Gpr43-deficient mice showed reduced weight loss and suppressed plasma lipoprotein lipase activity during fasting and eucaloric ketogenic diet feeding. Moreover, Gpr43-deficient mice exhibited minimal weight decrease after intermittent fasting. These observations provide insight into the role of ketone bodies in energy metabolism under shifts in nutrition and may contribute to the development of preventive medicine via diet and foods.
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Nosadini, R., C. Angelini, C. Trevisan, S. Vigili de Kreutzenberg, P. Fioretto, R. Trevisan, A. Avogaro, et al. "Glucose and ketone body turnover in carnitine-palmitoyl-transferase deficiency." Metabolism 36, no. 9 (September 1987): 821–26. http://dx.doi.org/10.1016/0026-0495(87)90088-6.
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Inokuchi, Toshiki, Kenji Imamura, Kayoko Nomura, Keiko Nomoto, and Sho Isogai. "Changes in carnitine metabolism with ketone body production in obese glucose-intolerant patients." Diabetes Research and Clinical Practice 30, no. 1 (October 1995): 1–7. http://dx.doi.org/10.1016/0168-8227(95)01140-4.
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Zheng, Jia-Lang, Zhi Luo, Mei-Qing Zhuo, Ya-Xiong Pan, Yu-Feng Song, Wei Hu, and Qi-Liang Chen. "Dietary l-carnitine supplementation increases lipid deposition in the liver and muscle of yellow catfish (Pelteobagrus fulvidraco) through changes in lipid metabolism." British Journal of Nutrition 112, no. 5 (June 16, 2014): 698–708. http://dx.doi.org/10.1017/s0007114514001378.
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Carnitine has been reported to improve growth performance and reduce body lipid content in fish. Thus, we hypothesised that carnitine supplementation can improve growth performance and reduce lipid content in the liver and muscle of yellow catfish (Pelteobagrus fulvidraco), a commonly cultured freshwater fish in inland China, and tested this hypothesis in the present study. Diets containing l-carnitine at three different concentrations of 47 mg/kg (control, without extra carnitine addition), 331 mg/kg (low carnitine) and 3495 mg/kg (high carnitine) diet were fed to yellow catfish for 8 weeks. The low-carnitine diet significantly improved weight gain (WG) and reduced the feed conversion ratio (FCR). In contrast, the high-carnitine diet did not affect WG and FCR. Compared with the control diet, the low-carnitine and high-carnitine diets increased lipid and carnitine contents in the liver and muscle. The increased lipid content in the liver could be attributed to the up-regulation of the mRNA levels of SREBP, PPARγ, fatty acid synthase (FAS) and ACCa and the increased activities of lipogenic enzymes (such as FAS, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and malic enzyme) and to the down-regulation of the mRNA levels of the lipolytic gene CPT1A. The increased lipid content in muscle could be attributed to the down-regulation of the mRNA levels of the lipolytic genes CPT1A and ATGL and the increased activity of lipoprotein lipase. In conclusion, in contrast to our hypothesis, dietary carnitine supplementation increased body lipid content in yellow catfish.
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Ozorio, Rodrigo O. A., Vincent J. T. Van Ginneken, Rui J. B. Bessa, Martin W. A. Verstegen, Johan A. J. Verreth, and Elbertus A. Huisman. "Effects of exercise on l-carnitine and lipid metabolism in African catfish (Clarias gariepinus) fed different dietary l-carnitine and lipid levels." British Journal of Nutrition 103, no. 8 (November 24, 2009): 1139–50. http://dx.doi.org/10.1017/s0007114509993035.
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African catfish (Clarias gariepinus) were fed four isonitrogenous diets (34 % crude protein), each containing one of two lipid (100 or 180 g/kg) and two l-carnitine (15 or 1000 mg/kg) levels. After 81 d of feeding, thirty-two fish (body weight 32 g) from each dietary group were randomly selected, sixteen fish were induced to a 3-h swim (speed of 1·5 body length (BL)/s), while the other sixteen fish were kept under resting condition. Fish fed 1000 mg l-carnitine accumulated 3·5 and 5 times more l-carnitine in plasma and muscle, respectively, than fish fed the 15 mg l-carnitine. Muscle l-carnitine content was significantly lower in exercised fish than in rested fish. High dietary lipid level (fish oil) led to an increase in muscle n-3 PUFA content and a decrease in SFA and MUFA content. In liver, the increase in dietary lipid level resulted in an increased levels of both n-6 and n-3 PUFA. l-carnitine supplementation significantly decreased n-3 PUFA content. Exercise decreased n-3 PUFA in both muscle and liver. Plasma lactate and lactate dehydrogenase, normally associated with increased glycolytic processes, were positively correlated with exercise and inversely correlated with dietary l-carnitine level. l-carnitine supplementation reduced significantly the RQ from 0·72 to 0·63, and an interaction between dietary l-carnitine and lipid was observed (P < 0·03). Our results indicate that an increase in fatty acids (FA) intake may promote FA oxidation, and both carnitine and exercise might influence the regulation of FA oxidation selectivity.
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Szekeres, Zsolt, Kalman Toth, and Eszter Szabados. "The Effects of SGLT2 Inhibitors on Lipid Metabolism." Metabolites 11, no. 2 (February 1, 2021): 87. http://dx.doi.org/10.3390/metabo11020087.
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Sodium glucose co-transporter 2 (SGLT2) inhibitors are effective antihyperglycemic agents by inhibiting glucose reabsorption in the proximal tubule of the kidney. Besides improving glycemic control in patients with type 2 diabetes, they also have additional favorable effects, such as lowering body weight and body fat. Several clinical studies have demonstrated their positive effect in reducing cardiovascular morbidity and mortality. Furthermore, the use of SGLT2 inhibitors were associated with fewer adverse renal outcomes comparing to other diabetic agents, substantiating their renoprotective effect in diabetic patients. SGLT2 inhibitors have also remarkable effect on lipid metabolism acting at different cellular levels. By decreasing the lipid accumulation, visceral and subcutaneous fat, they do not only decrease the body weight but also change body composition. They also regulate key molecules in lipid synthesis and transportation, and they affect the oxidation of fatty acids. Notably, they shift substrate utilization from carbohydrates to lipids and ketone bodies. In this review we intended to summarize the role of SGLT2 inhibitors in lipid metabolism especially on lipoprotein levels, lipid regulation, fat storage and substrate utilization.
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Wijkhuisen, A., F. Djouadi, J. Vilar, C. Merlet-Benichou, and J. Bastin. "Thyroid hormones regulate development of energy metabolism enzymes in rat proximal convoluted tubule." American Journal of Physiology-Renal Physiology 268, no. 4 (April 1, 1995): F634—F642. http://dx.doi.org/10.1152/ajprenal.1995.268.4.f634.
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Ketone bodies represent preferred energy substrates in the adult rat proximal tubule. They are abundant in the plasma of suckling rats and might represent an important oxidative substrate for the immature proximal tubule. The postnatal development of two enzymes involved in ketone body oxidation pathway, 3-ketoacid-CoA transferase and acetoacetyl-CoA thiolase, and of citrate synthase and carnitine acetyltransferase was studied in microdissected rat proximal convoluted tubule (PCT) at 1, 8, 16, and 21 days after birth. The enzyme levels in PCT of juxtamedullary and subcapsular nephrons were compared at 8, 16, and 21 days. A role of thyroid hormones in regulating the development of these enzymes was investigated by studying 8- and 21-day-old pups made hypothyroid by propylthiouracyl (PTU) treatment, as well as 21-day hyperthyroid rats. PTU treatment had no effect on enzyme activities on day 8. In contrast, the activity of all mitochondrial enzymes, except acetoacetyl-CoA thiolase, was significantly decreased in 21-day-old hypothyroid pups. In hypothyroid animals, the normal development of 3-ketoacid-CoA transferase, citrate synthase, and carnitine acetyltransferase could be restored after treatment by triiodothyronine (T3). In addition, one single injection of T3 to 8-day-old control pups induced a precocious rise in the activity of 3-ketoacid-CoA transferase, citrate synthase, and carnitine acetyltransferase in juxtamedullary PCT and in the activity of citrate synthase and carnitine acetyltransferase in subcapsular PCT. Altogether, these results point out the importance of the postnatal physiological rise in T3 in triggering the development of some mitochondrial oxidative enzymes in the PCT.
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Cahova, Monika, Petr Chrastina, Hana Hansikova, Zdenek Drahota, Jaroslava Trnovska, Vojtech Skop, Jana Spacilova, et al. "Carnitine supplementation alleviates lipid metabolism derangements and protects against oxidative stress in non-obese hereditary hypertriglyceridemic rats." Applied Physiology, Nutrition, and Metabolism 40, no. 3 (March 2015): 280–91. http://dx.doi.org/10.1139/apnm-2014-0163.
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The aim of this study was to estimate the effect of carnitine supplementation on lipid disorders and peripheral tissue insulin sensitivity in a non-obese animal model of insulin resistance, the hereditary hypertriglyceridemic (HHTg) rat. Male HHTg rats were fed a standard diet, and half of them received daily doses of carnitine (500 mg·kg−1body weight) for 8 weeks. Rats of the original Wistar strain were used for comparison. HHTg rats exhibited increased urinary excretion of free carnitine and reduced carnitine content in the liver and blood. Carnitine supplementation compensated for this shortage and promoted urinary excretion of acetylcarnitine without any signs of (acyl)carnitine accumulation in skeletal muscle. Compared with their untreated littermates, carnitine-treated HHTg rats exhibited lower weight gain, reduced liver steatosis, lower fasting triglyceridemia, and greater reduction of serum free fatty acid content after glucose load. Carnitine treatment was associated with increased mitochondrial biogenesis and oxidative capacity for fatty acids, amelioration of oxidative stress, and restored substrate switching in the liver. In skeletal muscle (diaphragm), carnitine supplementation was associated with significantly higher palmitate oxidation and a more favorable complete to incomplete oxidation products ratio. Carnitine supplementation further enhanced insulin sensitivity ex vivo. No effects on whole-body glucose tolerance were observed. Our data suggest that some metabolic syndrome-related disorders, particularly fatty acid oxidation, steatosis, and oxidative stress in the liver, could be attenuated by carnitine supplementation. The effect of carnitine could be explained, at least partly, by enhanced substrate oxidation and increased fatty acid transport from tissues in the form of short-chain acylcarnitines.
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Fukao, Toshiyuki, Gary D. Lopaschuk, and Grant A. Mitchell. "Pathways and control of ketone body metabolism: on the fringe of lipid biochemistry." Prostaglandins, Leukotrienes and Essential Fatty Acids 70, no. 3 (March 2004): 243–51. http://dx.doi.org/10.1016/j.plefa.2003.11.001.
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Ferrannini, E., G. Buzzigoli, S. Bevilacqua, C. Boni, D. Del Chiaro, M. Oleggini, L. Brandi, and F. Maccari. "Interaction of carnitine with insulin-stimulated glucose metabolism in humans." American Journal of Physiology-Endocrinology and Metabolism 255, no. 6 (December 1, 1988): E946—E952. http://dx.doi.org/10.1152/ajpendo.1988.255.6.e946.
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To characterize the interactions of carnitine with glucose metabolism, we administered L-carnitine as a primed (3 mmol) constant (17 mumol/min) intravenous infusion to healthy young volunteers during short-term (2 h) euglycemic hyperinsulinemia. In comparison with a control (saline) infusion, exogenous carnitine administration resulted in a stable, fourfold increase in basal serum carnitine levels (160 +/- 14 vs. 36 +/- 2 microM, P less than 0.001). At similar steady-state plasma insulin levels (75 microU/ml), carnitine infusion was associated with a 17 +/- 3% stimulation of whole body glucose utilization (6.56 +/- 0.60 vs. 5.57 +/- 0.44 mg.min-1.kg-1, P less than 0.001). This effect was more pronounced in the subjects with higher rates of glucose disposal (r = 0.65, P less than 0.05). Net rates of insulin-induced glucose oxidation (measured by continuous, computerized indirect calorimetry) were similar with or without carnitine (1.67 +/- 0.23 vs. 1.65 +/- 0.10 mg.min-1.kg-1, respectively). As a consequence, the carnitine-induced enhancement of total glucose metabolism was quantitatively accounted for by a 50% increase in nonoxidative glucose disposal (2.89 +/- 0.81 vs. 1.92 +/- 0.51 mg.min-1.kg-1, P less than 0.05). The inhibitory effect of insulin on net lipid oxidation was not altered by carnitine (-0.67 +/- 0.09 vs. -0.62 +/- 0.06 mg.min-1.kg-1). Circulating levels of free fatty acids (FFA), glycerol, and beta-hydroxybutyrate fell in parallel during insulin infusion in the test and control study, and blood lactate concentrations rose by similar amounts (approximately 0.35 mM).(ABSTRACT TRUNCATED AT 250 WORDS)
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Kim, Jun-dae, Teng Zhou, Aijun Zhang, Shumin Li, Anisha A. Gupte, Dale J. Hamilton, and Longhou Fang. "AIBP Regulates Metabolism of Ketone and Lipids but Not Mitochondrial Respiration." Cells 11, no. 22 (November 17, 2022): 3643. http://dx.doi.org/10.3390/cells11223643.
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Accumulating evidence indicates that the APOA1 binding protein (AIBP)—a secreted protein—plays a profound role in lipid metabolism. Interestingly, AIBP also functions as an NAD(P)H-hydrate epimerase to catalyze the interconversion of NAD(P)H hydrate [NAD(P)HX] epimers and is renamed as NAXE. Thus, we call it NAXE hereafter. We investigated its role in NAD(P)H-involved metabolism in murine cardiomyocytes, focusing on the metabolism of hexose, lipids, and amino acids as well as mitochondrial redox function. Unbiased metabolite profiling of cardiac tissue shows that NAXE knockout markedly upregulates the ketone body 3-hydroxybutyric acid (3-HB) and lipid-associated metabolites α-linolenic acid and deoxycholic acid. Paralleling greater ketone levels, ChemRICH analysis of the NAXE-regulated metabolites shows reduced abundance of hexose despite similar glucose levels in control and NAXE-deficient blood. NAXE knockout reduces cardiac lactic acid but has no effect on the content of other NAD(P)H-regulated metabolites, including those associated with glucose metabolism, the pentose phosphate pathway, or Krebs cycle flux. Although NAXE is present in mitochondria, it has no apparent effect on mitochondrial oxidative phosphorylation. Instead, we detected more metabolites that can potentially improve cardiac function (3-HB, adenosine, and α-linolenic acid) in the Naxe−/− heart; these mice also perform better in aerobic exercise. Our data reveal a new role of NAXE in cardiac ketone and lipid metabolism.
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A. Wohaieb, Saleh. "Effects of Allopurinol on Ketone Body Metabolism and Tissue Lipid Peroxidation in Alloxan Diabetes in Rats." Iraqi Journal of Pharmaceutical Sciences ( P-ISSN: 1683 - 3597 , E-ISSN : 2521 - 3512) 15, no. 1 (March 31, 2017): 37–42. http://dx.doi.org/10.31351/vol15iss1pp37-42.
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The aim of the present study is to investigate whether or not xanthine oxidase (XO)–derived reactive oxygen species (ROS) may play a role in the pathogenesis of alloxan (ALX)–induced diabetes in rats using the specific XO inhibitor and hydroxyl radical scavenger, allopurinol
The involvement of oxidative stress in ALX – diabetes was assessed by the measurement of plasma and various tissues lipid peroxides levels ( using thiobarbituric acid ( TBA ) reactive substances ). Furthermore, the ability of allopurinol to influence these and other biochemical parameters, including plasma and urine ketones levels were also investigated in diabetic rats.
Rats were divided into four groups: control, untreated diabetic, allopurinol – treated diabetic, and insulin – treated diabetics. At the end of the one week experimental period, blood and tissue samples were obtained from anesthesized animals for the measurement of the above – mentioned parameters.
Although the single intraperitoneal (i.p.) injection of allopurinol (25 mg/kg body wt.) 1h before or 1h after ALX injection (100 mg/kg body wt., i.p.) failed to prevent the induction of diabetes, it did lower ketonuria and the incidence of early ketosis–associated mortality in diabetic animals in comparison with non–allopurinol–treated diabetic rats. Subsequent administration of allopurinol (25 mg/kg body wt., i.p.) every 48 hr for 1wk (i.e., 3 additional doses) also decreased plasma ketone bodies levels as well as plasma and tissue (heart, liver, kidney, pancreas) lipid peroxides levels in comparison with non–allopurinol–treated diabetic rats. Daily insulin injection (9–12 U/kg body wt., S.C.) for 1wk period normalized all of the above–mentioned abnormalities.
The present results suggest that XO–derived ROS play a minor role (if any) in the diabetogenic effect of ALX. On the other hand, although the mechanism (s) underlying the protective effects of allopurinol on the diabetic state is presently unknown, these effects may reflect a possible association between impaired ketone body metabolism and lipid peroxidation: and suggest an effect of allopurinol on ketone body metabolism.
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Harvey, Kristin L., Lola E. Holcomb, and Stephen C. Kolwicz. "Ketogenic Diets and Exercise Performance." Nutrients 11, no. 10 (September 26, 2019): 2296. http://dx.doi.org/10.3390/nu11102296.
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The ketogenic diet (KD) has gained a resurgence in popularity due to its purported reputation for fighting obesity. The KD has also acquired attention as an alternative and/or supplemental method for producing energy in the form of ketone bodies. Recent scientific evidence highlights the KD as a promising strategy to treat obesity, diabetes, and cardiac dysfunction. In addition, studies support ketone body supplements as a potential method to induce ketosis and supply sustainable fuel sources to promote exercise performance. Despite the acceptance in the mainstream media, the KD remains controversial in the medical and scientific communities. Research suggests that the KD or ketone body supplementation may result in unexpected side effects, including altered blood lipid profiles, abnormal glucose homeostasis, increased adiposity, fatigue, and gastrointestinal distress. The purpose of this review article is to provide an overview of ketone body metabolism and a background on the KD and ketone body supplements in the context of obesity and exercise performance. The effectiveness of these dietary or supplementation strategies as a therapy for weight loss or as an ergogenic aid will be discussed. In addition, the recent evidence that indicates ketone body metabolism is a potential target for cardiac dysfunction will be reviewed.
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Schofield, P. S., T. J. French, and M. C. Sugden. "Ketone-body metabolism after surgical stress or partial hepatectomy. Evidence for decreased ketogenesis and a site of control distal to carnitine palmitoyltransferase I." Biochemical Journal 241, no. 2 (January 15, 1987): 475–81. http://dx.doi.org/10.1042/bj2410475.
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Rats were subjected to laparotomy, or laparotomy and partial hepatectomy, at 0-48 h before administration of water or medium-chain-length triacylglycerol, having been starved post-operatively. Functional hepatectomies were performed at intervals after the intragastric load. Blood ketone-body concentrations after medium-chain triacylglycerol administration and/or functional hepatectomy of these rats were compared with values obtained in starved control rats. Decreased ketonaemia in response to medium-chain triacylglycerol was observed for up to 48 h after partial hepatectomy and at 1 and 2 h after laparotomy, but not at 24 or 48 h after laparotomy. Rates of ketone-body clearance after functional hepatectomy were unaffected by prior laparotomy or partial hepatectomy. Ketonaemia after medium-chain-triacylglycerol administration was only partially blocked by inhibition of CPT I (carnitine palmitoyltransferase I). The results demonstrate sustained effects of partial hepatectomy and short-term effects of surgical stress to decrease ketonaemia via inhibition of ketogenesis at site(s) distal to CPT I.
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Mintz, Mark. "Carnitine in Human Immunodeficiency Virus Type 1 Infection/Acquired Immune Deficiency Syndrome." Journal of Child Neurology 10, no. 2_suppl (November 1995): 2S40–2S44. http://dx.doi.org/10.1177/0883073895010002s06.
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There is an increasing body of evidence that subgroups of patients infected with human immunodeficiency virus type 1 possess carnitine deficiency. Secondary carnitine deficiencies in these individuals may result from nutritional deficiencies, gastrointestinal disturbances, renal losses, or shifts in metabolic pathways. However, tissue depletion precipitated by drug toxicities, particularly zidovudine, is a major etiology and concern. Carnitine deficiency may impact on energy and lipid metabolism, causing mitochondrial and immune dysfunction. There are convincing laboratory data showing the in vitro ameliorative effects of L-carnitine supplementation on zidovudine-induced myopathies and lymphocyte function. Studies measuring the impact of L-carnitine supplementation on clinical characteristics are ongoing. (J Child Neurol 1995; 10(Suppl):2540-2544).
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Yuan, Junhua, Qixiao Jiang, Limin Song, Yuan Liu, Manwen Li, Qian Lin, Yanrun Li, et al. "L-Carnitine Is Involved in Hyperbaric Oxygen-Mediated Therapeutic Effects in High Fat Diet-Induced Lipid Metabolism Dysfunction." Molecules 25, no. 1 (January 1, 2020): 176. http://dx.doi.org/10.3390/molecules25010176.
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Lipid metabolism dysfunction and obesity are serious health issues to human beings. The current study investigated the effects of hyperbaric oxygen (HBO) against high fat diet (HFD)-induced lipid metabolism dysfunction and the roles of L-carnitine. C57/B6 mice were fed with HFD or normal chew diet, with or without HBO treatment. Histopathological methods were used to assess the adipose tissues, serum free fatty acid (FFA) levels were assessed with enzymatic methods, and the endogenous circulation and skeletal muscle L-carnitine levels were assessed with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Additionally, western blotting was used to assess the expression levels of PPARα, CPT1b, pHSL/HSL, and UCP1. HFD treatment increased body/adipose tissue weight, serum FFA levels, circulation L-carnitines and decreased skeletal muscle L-carnitine levels, while HBO treatment alleviated such changes. Moreover, HFD treatment increased fatty acid deposition in adipose tissues and decreased the expression of HSL, while HBO treatment alleviated such changes. Additionally, HFD treatment decreased the expression levels of PPARα and increased those of CPT1b in skeletal muscle, while HBO treatment effectively reverted such changes as well. In brown adipose tissues, HFD increased the expression of UCP1 and the phosphorylation of HSL, which was abolished by HBO treatment as well. In summary, HBO treatment may alleviate HFD-induced fatty acid metabolism dysfunction in C57/B6 mice, which seems to be associated with circulation and skeletal muscle L-carnitine levels and PPARα expression.
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Soeters, Maarten R., Peter B. Soeters, Marieke G. Schooneman, Sander M. Houten, and Johannes A. Romijn. "Adaptive reciprocity of lipid and glucose metabolism in human short-term starvation." American Journal of Physiology-Endocrinology and Metabolism 303, no. 12 (December 15, 2012): E1397—E1407. http://dx.doi.org/10.1152/ajpendo.00397.2012.
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The human organism has tools to cope with metabolic challenges like starvation that are crucial for survival. Lipolysis, lipid oxidation, ketone body synthesis, tailored endogenous glucose production and uptake, and decreased glucose oxidation serve to protect against excessive erosion of protein mass, which is the predominant supplier of carbon chains for synthesis of newly formed glucose. The starvation response shows that the adaptation to energy deficit is very effective and coordinated with different adaptations in different organs. From an evolutionary perspective, this lipid-induced effect on glucose oxidation and uptake is very strong and may therefore help to understand why insulin resistance in obesity and type 2 diabetes mellitus is difficult to treat. The importance of reciprocity in lipid and glucose metabolism during human starvation should be taken into account when studying lipid and glucose metabolism in general and in pathophysiological conditions in particular.
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Wicks, Shawna E., Bolormaa Vandanmagsar, Kimberly R. Haynie, Scott E. Fuller, Jaycob D. Warfel, Jacqueline M. Stephens, Miao Wang, et al. "Impaired mitochondrial fat oxidation induces adaptive remodeling of muscle metabolism." Proceedings of the National Academy of Sciences 112, no. 25 (June 8, 2015): E3300—E3309. http://dx.doi.org/10.1073/pnas.1418560112.
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The correlations between intramyocellular lipid (IMCL), decreased fatty acid oxidation (FAO), and insulin resistance have led to the hypothesis that impaired FAO causes accumulation of lipotoxic intermediates that inhibit muscle insulin signaling. Using a skeletal muscle-specific carnitine palmitoyltransferase-1 KO model, we show that prolonged and severe mitochondrial FAO inhibition results in increased carbohydrate utilization, along with reduced physical activity; increased circulating nonesterified fatty acids; and increased IMCLs, diacylglycerols, and ceramides. Perhaps more importantly, inhibition of mitochondrial FAO also initiates a local, adaptive response in muscle that invokes mitochondrial biogenesis, compensatory peroxisomal fat oxidation, and amino acid catabolism. Loss of its major fuel source (lipid) induces an energy deprivation response in muscle coordinated by signaling through AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) to maintain energy supply for locomotion and survival. At the whole-body level, these adaptations result in resistance to obesity.
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Brass, E. P., and R. A. Beyerinck. "Effects of propionate and carnitine on the hepatic oxidation of short- and medium-chain-length fatty acids." Biochemical Journal 250, no. 3 (March 15, 1988): 819–25. http://dx.doi.org/10.1042/bj2500819.
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Accumulation of propionate, or its metabolic product propionyl-CoA, can disrupt normal cellular metabolism. The present study examined the effects of propionate, or propionyl-CoA generated during the oxidation of odd-chain-length fatty acids, on hepatic oxidation of short- and medium-chain-length fatty acids. In isolated hepatocytes, ketone-body formation from odd-chain-length fatty acids was slow as compared with even-chain-length fatty acid substrates, and increased as the carbon chain length was increased from five to seven to nine. In contrast, rates of ketogenesis from butyrate, hexonoate and octanoate were all approximately equal. Propionate (10 mM) inhibited ketogenesis from butyrate, hexanoate and octanoate by 81%, 53% and 18% respectively. Addition of carnitine had no effect on ketogenesis from the even-chain-length fatty acids, but increased the rate of ketone-body formation from pentanoate (by 53%), heptanoate (by 28%) and from butyrate or hexanoate in the presence of propionate. The inhibitory effect of propionate could not be explained by shunting acetyl-CoA into the tricarboxylic acid cycle, as CO2 formation from butyrate was also decreased by propionate. Examination of the hepatocyte CoA pool during oxidation of butyrate demonstrated that addition of propionate decreased acetyl-CoA and CoA as propionyl-CoA accumulated. Addition of carnitine decreased propionyl-CoA by 50% (associated with production of propionylcarnitine) and increased acetyl-CoA and CoA. Similar changes in the CoA pool were seen during the oxidation of pentanoate. These results demonstrate that accumulation of propionyl-CoA results in inhibition of short-chain fatty acid oxidation. Carnitine can partially reverse this inhibition. Changes in the hepatocyte CoA pool are consistent with carnitine acting by generating propionylcarnitine, thereby decreasing propionyl-CoA and increasing availability of free CoA. The data provide further evidence of the potential cellular toxicity from organic acid accretion, and supports the concept that carnitine's interaction with the cellular CoA pool can have a beneficial effect on cellular metabolism and function under conditions of unusual organic acid accumulation.
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Kim, Jong-Yeon, Robert C. Hickner, Ronald L. Cortright, G. Lynis Dohm, and Joseph A. Houmard. "Lipid oxidation is reduced in obese human skeletal muscle." American Journal of Physiology-Endocrinology and Metabolism 279, no. 5 (November 1, 2000): E1039—E1044. http://dx.doi.org/10.1152/ajpendo.2000.279.5.e1039.
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The purpose of this study was to discern cellular mechanisms that contribute to the suppression of lipid oxidation in the skeletal muscle of obese individuals. Muscle was obtained from obese [body mass index (BMI), 38.3 ± 3.1 kg/m2] and lean (BMI, 23.8 ± 0.9 kg/m2) women, and fatty acid oxidation was studied by measuring 14CO2 production from14C-labeled fatty acids. Palmitate oxidation, which is at least partially dependent on carnitine palmitoyltransferase-1 (CPT-1) activity, was depressed ( P < 0.05) by ≈50% with obesity (6.8 ± 2.2 vs. 13.7 ± 1.4 nmole CO2 · g−1 · h−1). The CPT-1-independent event of palmitoyl carnitine oxidation was also depressed ( P < 0.01) by ≈45%. There were significant negative relationships ( P < 0.05) for adiposity with palmitate ( r = −0.76) and palmitoyl carnitine ( r = −0.82) oxidation. Muscle CPT-1 and citrate synthase activity, an index of mitochondrial content, were also significantly ( P < 0.05) reduced (≈35%) with obesity. CPT-1 ( r = −0.48) and citrate synthase ( r = −0.65) activities were significantly ( P < 0.05) related to adiposity. These data suggest that lesions at CPT-1 and post-CPT-1 events, such as mitochondrial content, contribute to the reduced reliance on fat oxidation evident in human skeletal muscle with obesity.
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Feingold, Kenneth R., Carl Grunfeld, Josef G. Heuer, Akanksha Gupta, Martin Cramer, Tonghai Zhang, Judy K. Shigenaga, et al. "FGF21 Is Increased by Inflammatory Stimuli and Protects Leptin-Deficient ob/ob Mice from the Toxicity of Sepsis." Endocrinology 153, no. 6 (April 2, 2012): 2689–700. http://dx.doi.org/10.1210/en.2011-1496.
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The acute phase response (APR) produces marked alterations in lipid and carbohydrate metabolism including decreasing plasma ketone levels. Fibroblast growth factor 21 (FGF21) is a recently discovered hormone that regulates lipid and glucose metabolism and stimulates ketogenesis. Here we demonstrate that lipopolysaccharide (LPS), zymosan, and turpentine, which induce the APR, increase serum FGF21 levels 2-fold. Although LPS, zymosan, and turpentine decrease the hepatic expression of FGF21, they increase FGF21 expression in adipose tissue and muscle, suggesting that extrahepatic tissues account for the increase in serum FGF21. After LPS administration, the characteristic decrease in plasma ketone levels is accentuated in FGF21−/− mice, but this is not due to differences in expression of carnitine palmitoyltransferase 1α or hydroxymethyglutaryl-CoA synthase 2 in liver, because LPS induces similar decreases in the expression of these genes in FGF21−/− and control mice. However, in FGF21−/− mice, the ability of LPS to increase plasma free fatty acid levels is blunted. This failure to increase plasma free fatty acid could contribute to the accentuated decrease in plasma ketone levels because the transport of fatty acids from adipose tissue to liver provides the substrate for ketogenesis. Treatment with exogenous FGF21 reduced the number of animals that die and the rapidity of death after LPS administration in leptin-deficient ob/ob mice and to a lesser extent in control mice. FGF21 also protected from the toxic effects of cecal ligation and puncture-induced sepsis. Thus, FGF21 is a positive APR protein that protects animals from the toxic effects of LPS and sepsis.
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Wu, Chih-Chung, Yu-Wen Huang, Chih-Yao Hou, Ya-Ting Chen, Cheng-Di Dong, Chiu-Wen Chen, Reeta-Rani Singhania, Jie-Yin Leang, and Shu-Ling Hsieh. "The Anti-Obesity Effects of Lemon Fermented Products in 3T3-L1 Preadipocytes and in a Rat Model with High-Calorie Diet-Induced Obesity." Nutrients 13, no. 8 (August 16, 2021): 2809. http://dx.doi.org/10.3390/nu13082809.
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Lemon (Citrus limon) has antioxidant, immunoregulatory, and blood lipid-lowering properties. This study aimed to determine the effect of the lemon fermented product (LFP) which is lemon fermented with Lactobacillus OPC1 to prevent obesity. The inhibition of lipid accumulation in 3T3-L1 adipocytes is examined using a Wistar rat model fed a high-fat diet to verify the anti-obesity efficacy and mechanism of LFP. Here, it was observed that LFP reduced cell proliferation and inhibited the lipid accumulation (8.3%) of 3T3-L1 adipocytes. Additionally, LFP reduced body weight (9.7%) and fat tissue weight (25.7%) of rats; reduced serum TG (17.0%), FFA (17.9%), glucose (29.3%) and ketone body (6.8%); and increased serum HDL-C (17.6%) and lipase activity (17.8%). LFP regulated the mRNA expression of genes related to lipid metabolism (PPARγ, C/EBPα, SREBP-1c, HSL, ATGL, FAS, and AMPK). Therefore, LFP reduces body weight and lipid accumulation by regulating the mRNA expression of genes related to lipid metabolism. Overall, our results implicate LFP as a potential dietary supplement for the prevention of obesity.
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Grunnet, N., J. Kondrup, and J. Dich. "Effect of ethanol on lipid metabolism in cultured hepatocytes." Biochemical Journal 228, no. 3 (June 15, 1985): 673–81. http://dx.doi.org/10.1042/bj2280673.
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Isolated rat hepatocytes were cultured in a modified HI-WO/BA medium for 16 h. In the following 24 h oleate or oleate plus ethanol was added to the medium. After this period the medium was changed again and the cultures were further incubated with [1-14C]oleate alone or with [1-14C]oleate plus ethanol for 6 h. This allowed a comparison of effects of short-term (6 h) and long-term (24 + 6 h) exposure to ethanol on fatty acid metabolism. The increased intracellular accumulation of triacylglycerol in the presence of ethanol was quantitatively accounted for by increased fatty acid uptake, by decreased fatty acid oxidation in the tricarboxylic acid cycle and by decreased VLDL (very-low-density lipoprotein)-triacylglycerol secretion. Ketone-body production was not affected. After short-term exposure the rate of accumulation of triacylglycerol was increased by 50%. This increase was accounted for by increased fatty acid uptake (44%), decreased tricarboxylic acid-cycle activity (49%) and decreased VLDL-triacylglycerol secretion (7%). After long-term exposure, the rate of accumulation of triacylglycerol was increased by 74%. This increase was accounted for by increased fatty acid uptake (34%), decreased tricarboxylic acid-cycle activity (34%) and decreased VLDL-triacylglycerol secretion (32%). The larger increase in accumulation of triacylglycerol after long-term exposure to ethanol was entirely accounted for by increased inhibition of secretion of VLDL-triacylglycerol. The biochemical mechanisms underlying the observations are discussed.
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Nesher, Elimelech, Hadas Fulman-Levy, Igor Koman, and Raichel Cohen-Harazi. "Abstract 3016: Beta-hydroxybutyrate alters lipid metabolism affecting oncogenicity of MCF7 cells." Cancer Research 82, no. 12_Supplement (June 15, 2022): 3016. http://dx.doi.org/10.1158/1538-7445.am2022-3016.
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Abstract The ketogenic diet, based on high fat (over 70% of daily calories), low carbohydrate, and adequate protein intake, has become popular due to its potential therapeutic benefits for several diseases including cancer. Recent evidence suggests ketogenic metabolic therapy as a complementary or alternative approach to breast cancer treatment. Under ketogenic conditions, as in starvation, the levels of glucose, insulin, and insulin-like growth factors in the blood decrease and stabilize, and the liver produces ketone bodies, acetone, acetoacetate (AcA) and β-hydroxybutyrate (ΒHb) by beta-oxidation of fatty acids, as an alternative energy source. Due to the volatile nature of acetone and its instability in the blood, acetone has no effect on cancer cells under physiological conditions. AcA alone is unstable as well, and is used in research as a sodium or lithium salt. Despite the widely accepted use of lithium AcA as a ketone body source, we and others recently demonstrated that its cytotoxic effects result from the lithium and not from acetoacetate.In this study, we aimed to elucidate the effect of the third ketone body, ΒHb, on breast cancer cells in vitro. Using two cancer (MCF7 and MDA-MB-231) and one non-cancer (HB2) breast cell lines, we evaluated the effect of β-hydroxybutyrate treatment on cell growth parameters and assessed the effect of BHb on metabolism and the gene expression profile. We found that ΒHb increases viability and proliferation of MCF7, but has no affect MDA-MB-231 and non-cancer HB2 cell viability. We observed no changes in glucose intake or lactate output following BHb treatment, but an increase in ROS level was detected. Gene expression analysis revealed a differential effect of BHb treatment on changes in genes involved in lipid metabolism and oxidative phosphorylation, among the tested cell lines. While genes involved in lipid metabolism were downregulated in MCF7 cells, ΒHb mitochondrial monocarboxylate transporter-4 (MCT4) expression was found to be significantly upregulated in both cancer cell lines with 10mM BHb but not affected in non-cancer breast cells. 3-hydroxybutyrate dehydrogenase 1 (BDH1) and 3-oxoacid CoA-transferase 1 (OXCT1), enzymes involved in BHb oxidation in the mitochondria, were significantly increased in MCF7 with a non-significant trend toward upregulation in MDA-MB-231 cells. Treatment of MCF7 cells with 10mM of BHb also significantly downregulated AMP-activated protein kinase (AMPK) and upregulated HDAC1, both known to be involved in BHb metabolism. Based on our results, we conclude that differential response of breast cell lines to BHb treatment, as alternative energy source or signal to altered lipid metabolism and oncogenicity, supports the need for a personalized approach to breast cancer patient treatment. Citation Format: Elimelech Nesher, Hadas Fulman-Levy, Igor Koman, Raichel Cohen-Harazi. Beta-hydroxybutyrate alters lipid metabolism affecting oncogenicity of MCF7 cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3016.
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Levy, James R., Byrd Davenport, John N. Clore, and Wayne Stevens. "Lipid metabolism and resistin gene expression in insulin-resistant Fischer 344 rats." American Journal of Physiology-Endocrinology and Metabolism 282, no. 3 (March 1, 2002): E626—E633. http://dx.doi.org/10.1152/ajpendo.00346.2001.
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The interrelationship between insulin and leptin resistance in young Fischer 344 (F344) rats was studied. Young F344 and Sprague-Dawley (SD) rats were fed regular chow. F344 animals had two- to threefold higher insulin and triglyceride concentrations and increased stores of triglycerides within liver and muscle. F344 animals gained more body fat. Both acyl-CoA oxidase (ACO) and carnitine palmitoyltransferase I gene expression were 20–50% less in F344 animals than in age-matched SD animals. Peroxisome proliferator-activated receptor-α gene expression was reduced in 70-day-old F344 animals. Finally, resistin gene expression was similar in 70-day-old SD and F344 animals. Resistin gene expression increased fivefold in F344 animals and twofold in SD animals from 70 to 130 days, without a change in insulin sensitivity. We conclude that young F344 animals have both insulin and leptin resistance, which may lead to diminished fatty oxidation and accumulation of triglycerides in insulin-sensitive target tissues. We did not detect a role for resistin in the etiology of insulin resistance in F344 animals.
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Duncan, WP, and JL Marcon. "Enzymes of energy metabolism in hatchlings of amazonian freshwater turtles (Testudines, Podocnemididae)." Brazilian Journal of Biology 69, no. 2 (May 2009): 319–25. http://dx.doi.org/10.1590/s1519-69842009000200012.
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The metabolic profiles of selected tissues were analyzed in hatchlings of the Amazonian freshwater turtles Podocnemis expansa, P. unifilis and P. sextuberculata. Metabolic design in these species was judged based on the key enzymes of energy metabolism, with special emphasis on carbohydrate, lipid, amino acid and ketone body metabolism. All species showed a high glycolytic potential in all sampled tissues. Based on low levels of hexokinase, glycogen may be an important fuel for these species. The high lactate dehydrogenase activity in the liver may play a significant role in carbohydrate catabolism, possibly during diving. Oxidative metabolism in P. sextuberculata appears to be designed for the use of lipids, amino acids and ketone bodies. The maximal activities of 3-hydroxyacyl-CoA dehydrogenase, malate dehydrogenase, glutamine dehydrogenase, alanine aminotransferase and succinyl-CoA keto transferase display high aerobic potential, especially in muscle and liver tissues of this species. Although amino acids and ketone bodies may be important fuels for oxidative metabolism, carbohydrates and lipids are the major fuels used by P. expansa and P. unifilis. Our results are consistent with the food habits and lifestyle of Amazonian freshwater turtles. The metabolic design, based on enzyme activities, suggests that hatchlings of P. unifilis and P. expansa are predominately herbivorous, whereas P. sextuberculata rely on a mixed diet of animal matter and vegetation.
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Holness, M. J., T. N. Palmer, and M. C. Sugden. "Effects of administration of tri-iodothyronine on the response of cardiac and renal pyruvate dehydrogenase complex to starvation for 48 h." Biochemical Journal 232, no. 1 (November 15, 1985): 255–59. http://dx.doi.org/10.1042/bj2320255.
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Effects of administration of tri-iodothyronine (T3) on activities of cardiac and renal pyruvate dehydrogenase complex (active form, PDHa) were investigated. In fed rats, T3 treatment did not affect cardiac or renal PDHa activity, although blood non-esterified fatty acid and ketone-body concentrations were increased. Starvation (48 h) of both control and T3-treated rats resulted in similar increases in the steady-state concentrations of fatty acids and ketone bodies, but inactivation of cardiac and renal pyruvate dehydrogenase complex activities was diminished by T3 treatment. Inhibition of lipolysis increased renal and cardiac PDHa in control but not in T3-treated 48 h-starved rats, despite decreased fatty acid and ketone-body concentrations in both groups. The results suggest that hyperthyroidism influences the response of cardiac and renal PDHa activities to starvation through changes in the metabolism of lipid fuels in these tissues.
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Newsholme, P., R. Curi, S. Gordon, and E. A. Newsholme. "Metabolism of glucose, glutamine, long-chain fatty acids and ketone bodies by murine macrophages." Biochemical Journal 239, no. 1 (October 1, 1986): 121–25. http://dx.doi.org/10.1042/bj2390121.
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Maximum activities of some key enzymes of metabolism were studied in elicited (inflammatory) macrophages of the mouse and lymph-node lymphocytes of the rat. The activity of hexokinase in the macrophage is very high, as high as that in any other major tissue of the body, and higher than that of phosphorylase or 6-phosphofructokinase, suggesting that glucose is a more important fuel than glycogen and that the pentose phosphate pathway is also important in these cells. The latter suggestion is supported by the high activities of both glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. However, the rate of glucose utilization by ‘resting’ macrophages incubated in vitro is less than the 10% of the activity of 6-phosphofructokinase: this suggests that the rate of glycolysis is increased dramatically during phagocytosis or increased secretory activity. The macrophages possess higher activities of citrate synthase and oxoglutarate dehydrogenase than do lymphocytes, suggesting that the tricarboxylic acid cycle may be important in energy generation in these cells. The activity of 3-oxoacid CoA-transferase is higher in the macrophage, but that of 3-hydroxybutyrate dehydrogenase is very much lower than those in the lymphocytes. The activity of carnitine palmitoyltransferase is higher in macrophages, suggesting that fatty acids as well as acetoacetate could provide acetyl-CoA as substrate for the tricarboxylic acid cycle. No detectable rate of acetoacetate or 3-hydroxybutyrate utilization was observed during incubation of resting macrophages, but that of oleate was 1.0 nmol/h per mg of protein or about 2.2% of the activity of palmitoyltransferase. The activity of glutaminase is about 4-fold higher in macrophages than in lymphocytes, which suggests that the rate of glutamine utilization could be very high. The rate of utilization of glutamine by resting incubated macrophages was similar to that reported for rat lymphocytes, but was considerably lower than the activity of glutaminase.
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Marquis, Bryce J., Eugenia Carvahlo, Nicholas Hurren, Robert R. Wolfe, and Elisabet Borsheim. "2275." Journal of Clinical and Translational Science 1, S1 (September 2017): 5. http://dx.doi.org/10.1017/cts.2017.33.
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OBJECTIVES/SPECIFIC AIMS: This study will assess the effect of essential amino acid (EAA) supplementation on plasma triglyceride (TG) in elderly adults. We will also explore the mechanisms mediating EAA mediated changes in fat metabolism and to suggest promising routes to refine therapy of hypertriglyceridemia. METHODS/STUDY POPULATION: In total, 7 nondiabetic male and female subjects ages 50–75 years with elevated plasma TG levels (130–500 mg/dL) were recruited to participate in an acute (5 h) and long-term (8 wk) EAA supplementation study. We measured changes in regional and whole body fat metabolism, including changes in body composition, plasma TG levels, whole body fat metabolic rates, tissue mitochondrial respiratory capacity, and metabolomic profiles before and after supplementation. RESULTS/ANTICIPATED RESULTS: Long-term EAA supplementation decreased fasted plasma TG levels by 19% (p<0.01). Metabolomics of skeletal muscle found acute EAA supplementation resulted in increased EAA metabolic products while long-term supplementation resulted in increased anaplerosis [flux into the tricarboxylic acid cycle (TCA) intermediate pool] and anaplerotic substrates [propionyl (p<0.01) and succinyl (p<0.01) carnitine] and intermediates of long-chain fatty acid metabolism [stearoyl (p<0.01) and myristoyl (p<0.05) carnitine]. However, tissue level respiratory capacity appeared to be unaffected by EAA supplementation. DISCUSSION/SIGNIFICANCE OF IMPACT: EAA supplementation has potential to improve lipid metabolism and plasma TG levels in non-diabetic older adults. Mitochondrial metabolomics suggest that insufficient TCA pool size may limit tissue fatty acid oxidation and may provide an additional route for nutritional therapy.
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Berneis, Kaspar, Ronald Ninnis, Dieter Häussinger, and Ulrich Keller. "Effects of hyper- and hypoosmolality on whole body protein and glucose kinetics in humans." American Journal of Physiology-Endocrinology and Metabolism 276, no. 1 (January 1, 1999): E188—E195. http://dx.doi.org/10.1152/ajpendo.1999.276.1.e188.
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To investigate the effect of acute changes of extracellular osmolality on whole body protein and glucose metabolism, we studied 10 male subjects during three conditions: hyperosmolality was induced by fluid restriction and intravenous infusion of hypertonic NaCl [2–5%; (wt/vol)] during 17 h; hypoosmolality was produced by intravenous administration of desmopressin, liberal water drinking, and infusion of hypotonic saline (0.4%); and the isoosmolality study consisted of ad libitum oral water intake by the subjects. Leucine flux ([1-13C]leucine infusion technique), a parameter of whole body protein breakdown, decreased during the hypoosmolality study ( P < 0.02 vs. isoosmolality). The leucine oxidation rate decreased during the hypoosmolality study ( P < 0.005 vs. isoosmolality). Metabolic clearance rate of glucose during hyperinsulinemic-euglycemic clamping increased less during the hypoosmolality study than during the isoosmolality study ( P < 0.04). Plasma insulin decreased, and plasma nonesterified fatty acids, glycerol, and ketone body concentrations and lipid oxidation increased during the hypoosmolality study. It is concluded that acute alterations of plasma osmolality influence whole body protein, glucose, and lipid metabolism; hypoosmolality results in protein sparing associated with increased lipolysis and lipid oxidation and impaired insulin sensitivity.
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Berthiaume, Magalie, Mathieu Laplante, William Festuccia, Yves Gélinas, Sébastien Poulin, Josée Lalonde, Denis R. Joanisse, Rolf Thieringer, and Yves Deshaies. "Depot-Specific Modulation of Rat Intraabdominal Adipose Tissue Lipid Metabolism by Pharmacological Inhibition of 11β-Hydroxysteroid Dehydrogenase Type 1." Endocrinology 148, no. 5 (May 1, 2007): 2391–97. http://dx.doi.org/10.1210/en.2006-1199.
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The metabolic consequences of visceral obesity have been associated with amplification of glucocorticoid action by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in adipose tissue. This study aimed to assess in a rat model of diet-induced obesity the effects of pharmacological 11β-HSD1 inhibition on the morphology and expression of key genes of lipid metabolism in intraabdominal adipose depots. Rats fed a high-sucrose, high-fat diet were treated or not with a specific 11β-HSD1 inhibitor (compound A, 3 mg/kg·d) for 3 wk. Compound A did not alter food intake or body weight gain but specifically reduced mesenteric adipose weight (−18%) and adipocyte size, without significantly affecting those of epididymal or retroperitoneal depots. In mesenteric fat, the inhibitor decreased (to 25–50% of control) mRNA levels of genes involved in lipid synthesis (FAS, SCD1, DGAT1) and fatty acid cycling (lipolysis/reesterification, ATGL and PEPCK) and increased (30%) the activity of the fatty acid oxidation-promoting enzyme carnitine palmitoyltransferase 1. In striking contrast, in the epididymal depot, 11β-HSD1 inhibition increased (1.5–5-fold) mRNA levels of those genes related to lipid synthesis/cycling and slightly decreased carnitine palmitoyltransferase 1 activity, whereas gene expression remained unaffected in the retroperitoneal depot. Compound A robustly reduced liver triacylglycerol content and plasma lipids. The study demonstrates that pharmacological inhibition of 11β-HSD1, at a dose that does not alter food intake, reduces fat accretion specifically in the mesenterical adipose depot, exerts divergent intraabdominal depot-specific effects on genes of lipid metabolism, and reduces steatosis and lipemia.
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Efimenko, Natalia V., Valentina F. Reps, Anna V. Abramtsova, and Tatyana M. Simonova. "The prospect of using L-carnitine for modification of drinking mineral waters in order to increase their metabolic potential." Russian Journal of Physiotherapy, Balneology and Rehabilitation 20, no. 3 (May 15, 2021): 263–71. http://dx.doi.org/10.17816/1681-3456-2021-20-263-271.
Full textAbstract:
Currently, a search is underway for non-drug biologically active agents that help restore impaired metabolism in metabolic syndrome. The attention of many researchers is drawn to L-carnitine and its role in the metabolism of fats and carbohydrates in both normal and pathological conditions.
The review is devoted to an urgent topic the theoretical justification of increasing the biogenic potential of drinking mineral waters in order to use them in the non-drug treatment of metabolic syndrome. The choice of a biologically active substance for the modification of drinking mineral waters, namely, L-carnitine, is based on its direct involvement in the energy exchange of body cells.
L-carnitine plays an irreplaceable role in lipid metabolism: it participates in the transport of fatty acids and products of their incomplete oxidation across the mitochondrial membrane, potentiating -oxidation of long-chain fatty acids, which leads to the activation of energy metabolism in various tissues. Thus, it can be assumed that the addition of L-carnitine to the diet of patients with metabolic syndrome and type 2 diabetes mellitus may be an effective tool in the treatment and prevention of the progression of these diseases.
The data of experimental and clinical studies justifying the preventive effect of drinking mineral waters were analyzed. In addition, we have conducted searching for scientific publications over the past 5 years in the electronic databases PubMed, Web of Science, e-Library on the study of L-carnitine and drinking mineral waters of various compositions, taking into account their influence on the components of metabolic syndrome. The search terms provided criteria that included full text, related data, clinical trials, meta-analysis, randomized controlled trials, and systematic reviews.
Based on the results of independent scientific studies, it is unambiguous to conclude that there is both a direct (due to dissolved ions) and a more complex (mediated through regulatory systems) effect of mineral waters on impaired metabolism caused by magnesium and calcium deficiency in this group of patients.
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Duerden, Julia M., and C. J. Bates. "Effect of riboflavin deficiency on lipid metabolism of liver and brown adipose tissue of sucking rat pups." British Journal of Nutrition 53, no. 1 (January 1985): 107–15. http://dx.doi.org/10.1079/bjn19850015.
Full textAbstract:
1. An increase in 1iver:body-weight and in hepatic triacylglycerol content, together with changes in the fatty acid profiles of hepatic phospholipids, were observed as a result of moderate riboflavin deficiency in sucking rat pups. Oxygen consumption by hepatic mitochondria, with palmitoyl L-carnitine as substrate, was not significantly impaired.2. Mitochondria from interscapular brown adipose tissue, however, showed a marked impairment of O2 Consumption, with palmitoyl L-carnitine as substrate, in the riboflavin-deficient pups. This impairment was also apparent after uncoupling with carbonyl cyanide p-trifluoromethoxyphenylhydrazone, but was not consistently observed after the addition of GDP to suppress uncoupled oxidation. It was much less evident, and did not reach statistical significance, for the mitochondria of brown adipose tissue of the corresponding deficient dams.3. Binding of 3H-labe11ed GDP by brown adipose tissue mitochondria was unaffected by riboflavin deficiency in the pups, suggesting that the effect on O2 consumption is more likely to be due to impaired integrity of the mitochondrial respiratory chain, than to impairment of the specific capacity for uncoupling of respiration which is characteristic of brown adipose tissue mitochondria. Total cytochrome c oxidase (EC 1.9.3.1) activity of the brown adipose tissue of riboflavin-deficient pups was not significantly reduced.4. A small but significant impairment was observed in the stimulation ofwhole-body O2consumption by injected noradrenaline in the riboflavin-deficient pups, suggesting that the impairment of brown adipose tissue mitochondrial function may be accompanied by impaired physiological capacity in vivo.
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Foretz, Marc, Patrick Even, and Benoit Viollet. "AMPK Activation Reduces Hepatic Lipid Content by Increasing Fat Oxidation In Vivo." International Journal of Molecular Sciences 19, no. 9 (September 19, 2018): 2826. http://dx.doi.org/10.3390/ijms19092826.
Full textAbstract:
The energy sensor AMP-activated protein kinase (AMPK) is a key player in the control of energy metabolism. AMPK regulates hepatic lipid metabolism through the phosphorylation of its well-recognized downstream target acetyl CoA carboxylase (ACC). Although AMPK activation is proposed to lower hepatic triglyceride (TG) content via the inhibition of ACC to cause inhibition of de novo lipogenesis and stimulation of fatty acid oxidation (FAO), its contribution to the inhibition of FAO in vivo has been recently questioned. We generated a mouse model of AMPK activation specifically in the liver, achieved by expression of a constitutively active AMPK using adenoviral delivery. Indirect calorimetry studies revealed that liver-specific AMPK activation is sufficient to induce a reduction in the respiratory exchange ratio and an increase in FAO rates in vivo. This led to a more rapid metabolic switch from carbohydrate to lipid oxidation during the transition from fed to fasting. Finally, mice with chronic AMPK activation in the liver display high fat oxidation capacity evidenced by increased [C14]-palmitate oxidation and ketone body production leading to reduced hepatic TG content and body adiposity. Our findings suggest a role for hepatic AMPK in the remodeling of lipid metabolism between the liver and adipose tissue.
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Yang, Q., Y. Mao, J. Wang, H. Yu, X. Zhang, X. Pei, Z. Duan, C. Xiao, and M. Ma. "Gestational bisphenol A exposure impairs hepatic lipid metabolism by altering mTOR/CRTC2/SREBP1 in male rat offspring." Human & Experimental Toxicology 41 (January 2022): 096032712211298. http://dx.doi.org/10.1177/09603271221129852.
Full textAbstract:
Lipid metabolism is an important biochemical process in the body. Recent studies have found that environmental endocrine disruptors play an important role in the regulation of lipid metabolism. Bisphenol A (BPA), a common environmental endocrine disruptor, has adverse effects on lipid metabolism, but the mechanism is still unclear. This study aimed to investigate the effects of gestational BPA exposure on hepatic lipid metabolism and its possible mechanism in male offspring. The pregnant Sprague-Dawley rats were exposed to BPA (0, 0.05, 0.5, 5 mg/kg/day) from day 5 to day 19 of gestation to investigate the levels of triglyceride (TG) and total cholesterol (TC), and the expression of liver lipid metabolism-related genes in male offspring rats. The results showed that compared with the control group, the TG and TC levels in serum and liver in BPA-exposed groups was increased. And the expressions of liver fatty acid oxidation related genes, such as peroxisome proliferators-activated receptor α (PPARα) and carnitine palmitoyl transferase 1α (CPT1α), were down-regulated. However, the expressions of fatty acid synthesis related genes, such as sterol regulatory element binding proteins 1 (SREBP-1), acetyl-CoA carboxylase 1 (ACC1), fatty acid synthase (FAS) and stearoyl-CoA desaturase 1 (SCD-1), were up-regulated. The increased protein levels of mTOR and p-CRTC2 suggested that CREB-regulated transcription coactivator 2 (CRTC2) might be an important mediator in the mTOR/SREBP-1 pathway. In conclusion, these results demonstrated that mTOR/CRTC2/SREBP-1 could be affected by gestational BPA exposure, which may involve in the lipid metabolic disorders in later life.
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Salic, Kanita, Eveline Gart, Florine Seidel, Lars Verschuren, Martien Caspers, Wim van Duyvenvoorde, Kari E. Wong, et al. "Combined Treatment with L-Carnitine and Nicotinamide Riboside Improves Hepatic Metabolism and Attenuates Obesity and Liver Steatosis." International Journal of Molecular Sciences 20, no. 18 (September 5, 2019): 4359. http://dx.doi.org/10.3390/ijms20184359.
Full textAbstract:
Obesity characterized by adiposity and ectopic fat accumulation is associated with the development of non-alcoholic fatty liver disease (NAFLD). Treatments that stimulate lipid utilization may prevent the development of obesity and comorbidities. This study evaluated the potential anti-obesogenic hepatoprotective effects of combined treatment with L-carnitine and nicotinamide riboside, i.e., components that can enhance fatty acid transfer across the inner mitochondrial membrane and increase nicotinamide adenine nucleotide (NAD+) levels, which are necessary for β-oxidation and the TCA cycle, respectively. Ldlr −/−.Leiden mice were treated with high-fat diet (HFD) supplemented with L-carnitine (LC; 0.4% w/w), nicotinamide riboside (NR; 0.3% w/w) or both (COMBI) for 21 weeks. L-carnitine plasma levels were reduced by HFD and normalized by LC. NR supplementation raised its plasma metabolite levels demonstrating effective delivery. Although food intake and ambulatory activity were comparable in all groups, COMBI treatment significantly attenuated HFD-induced body weight gain, fat mass gain (−17%) and hepatic steatosis (−22%). Also, NR and COMBI reduced hepatic 4-hydroxynonenal adducts. Upstream-regulator gene analysis demonstrated that COMBI reversed detrimental effects of HFD on liver metabolism pathways and associated regulators, e.g., ACOX, SCAP, SREBF, PPARGC1B, and INSR. Combination treatment with LC and NR exerts protective effects on metabolic pathways and constitutes a new approach to attenuate HFD-induced obesity and NAFLD.
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Sheikh, Kashif, Germán Camejo, Boel Lanne, Torbjörn Halvarsson, Marie Rydén Landergren, and Nicholas D. Oakes. "Beyond lipids, pharmacological PPARα activation has important effects on amino acid metabolism as studied in the rat." American Journal of Physiology-Endocrinology and Metabolism 292, no. 4 (April 2007): E1157—E1165. http://dx.doi.org/10.1152/ajpendo.00254.2006.
Full textAbstract:
PPARα agonists have been characterized largely in terms of their effects on lipids and glucose metabolism, whereas little has been reported about effects on amino acid metabolism. We studied responses to the PPARα agonist WY 14,643 (30 μmol·kg−1·day−1 for 4 wk) in rats fed a saturated fat diet. Plasma and urine were analyzed with proton NMR. Plasma amino acids were measured using HPLC, and hepatic gene expression was assessed with DNA arrays. The high-fat diet elevated plasma levels of insulin and triglycerides (TG), and WY 14,643 treatment ameliorated this insulin resistance and dyslipidemia, lowering plasma insulin and TG levels. In addition, treatment decreased body weight gain, without altering cumulative food intake, and increased liver mass. WY 14,643 increased plasma levels of 12 of 22 amino acids, including glucogenic and some ketogenic amino acids, whereas arginine was significantly decreased. There was no alteration in branched-chain amino acid levels. Compared with the fat-fed control animals, WY 14,643-treated animals had raised plasma urea and ammonia levels as well as raised urine levels of N-methylnicotinamide and dimethylglycine. WY 14,643 induced changes in a number of key genes involved in amino acid metabolism in addition to expected effects on hepatic genes involved in lipid catabolism and ketone body formation. In conclusion, the present results suggest that, in rodents, effects of pharmacological PPARα activation extend beyond control of lipid metabolism to include important effects on whole body amino acid mobilization and hepatic amino acid metabolism.
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Sá, Carla, Ana Rita Oliveira, Cátia Machado, Marisa Azevedo, and Cristina Pereira-Wilson. "Effects on Liver Lipid Metabolism of the Naturally Occurring Dietary Flavone Luteolin-7-glucoside." Evidence-Based Complementary and Alternative Medicine 2015 (2015): 1–9. http://dx.doi.org/10.1155/2015/647832.
Full textAbstract:
Disruptions in whole-body lipid metabolism can lead to the onset of several pathologies such as nonalcoholic fatty liver disease (NAFLD) and cardiovascular diseases (CVDs). The present study aimed at elucidating the molecular mechanisms behind the lipid-lowering effects of the flavone luteolin-7-glucoside (L7G) which we previously showed to improve plasma lipid profile in rats. L7G is abundant in plant foods of Mediterranean diet such as aromatic plants used as herbs. Results show that dietary supplementation with L7G for one week induced the expression of peroxisome proliferator-activated receptor-alpha (PPAR-α) and of its target gene carnitine palmitoyl transferase 1 (CPT-1) in rat liver. L7G showed a tendency to decrease the hepatic expression of sterol regulatory element-binding protein-1 (SREBP-1), without affecting fatty acid synthase (FAS) protein levels. Although SREBP-2 and LDLr mRNA levels did not change, the expression of HMG CoA reductase (HMGCR) was significantly repressed by L7G. L7G also inhibited this enzyme’sin vitroactivity in a dose dependent manner, but only at high and not physiologically relevant concentrations. These results add new evidence that the flavone luteolin-7-glucoside may help in preventing metabolic diseases and clarify the mechanisms underlying the beneficial health effects of diets rich in fruits and vegetables.
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Driedzic, William R., Heidi L. Crowe, Peter W. Hicklin, and Dawn H. Sephton. "Adaptations in pectoralis muscle, heart mass, and energy metabolism during premigratory fattening in semipalmated sandpipers (Calidris pusilla)." Canadian Journal of Zoology 71, no. 8 (August 1, 1993): 1602–8. http://dx.doi.org/10.1139/z93-226.
Full textAbstract:
In late summer, semipalmated sandpipers (Calidris pusilla) migrate nonstop from eastern Canada to wintering sites on the northwest coast of South America. Before their transoceanic flight, the birds feed intensively for about 15 days during which time lipids are stored. The fat-free dry mass of the pectoralis muscle increases during the fattening period, probably increasing the maximal power output of the muscle. Plasma free fatty acids and triglycerides, pectoralis muscle lipid content, and the activity of carnitine oleoyl coenzyme A transferase are higher in heavy (fat) than in light (lean) birds. These alterations imply an enhanced capacity to utilize fatty acids as a metabolic fuel during migration. Total pectoralis muscle glycogen levels and the activity of pyruvate kinase increase, suggesting a higher capacity for glycogenolysis, which may be important during intense levels of energy demand. Heart size and protein content per gram of tissue increase in association with an increase in body mass. However, total levels of key mitochondrial enzymes, citrate synthase and carnitine oleoyl coenzyme A transferase, do not change, suggesting that in the heart an increase in total protein content occurs without an increase in mitochondrial proteins.
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Özer, Şehriban Duyar, and Makbule Gezmen Karadağ. "The Association Between Serum Carnitine Level, Glucose Regulation, Body Fat and Nutrient Intake in Diabetic Individuals." EuroBiotech Journal 5, no. 2 (April 1, 2021): 92–99. http://dx.doi.org/10.2478/ebtj-2021-0013.
Full textAbstract:
Abstract Carnitine (β-hydroxy-γ-trimethyl amino butyrate) is, a vitamin-like substance carrying long-chain fatty acids into the mitochondrial matrix. Due to its effect in energy metabolism, carnitine plays an important role in controlling diabetes and its complications. Studies on this topic have often focused on carnitine supplementation. This study was planned to investigate the relationship between serum carnitine level, glucose regulation and body fat in diabetic patients. A total of 64 people between the ages of 30-5, 32 patients with type 2 diabetes and 32 healthy subjects, were included in the study. Individual lipid profiles, glucose, insulin and serum carnitine levels were analyzed, anthropometric measurements were taken and 24-hour recall food consumption was recorded. As a result, blood glucose, insulin, triglyceride, VLDL-C, HDL-C and HOMA-IR were found to be higher in diabetic individuals than healthy group (p<0,05). Serum carnitine levels were found to be significantly lower in diabetic male (50,6±20,83 nmol/mL) than in healthy male (59,5±17,25 nmol/mL)(p<0,05). This difference was not statistically significant among female (p>0,05). It has been observed that intake of energy and macronutrients of diabetic individuals is generally lower than that of healthy individuals. Serum carnitine level was positively associated with polyunsaturated fatty acids and omega-6 fatty acid intake in male in the healthy group showed a negative correlation with fiber intake in female in the healthy group (p<0,05). There were negative correlations between serum carnitine level with body weight, body mass index and body fat mass in female in the healthy group (p<0,05). Individuals with diabetes are predisposed to dyslipidemia and insulin resistance. As a result; food consumption, and body fat affect individuals’ serum carnitine levels in type-2 diabetes. Since there is not enough study evaluating the relationship between anthropometric measurements of individuals and serum carnitine levels, it is thought that this result will guide future studies.
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Woo, Minji, Yeong Song, Keon-Hee Kang, and Jeong Noh. "Anti-Obesity Effects of Collagen Peptide Derived from Skate (Raja kenojei) Skin Through Regulation of Lipid Metabolism." Marine Drugs 16, no. 9 (August 30, 2018): 306. http://dx.doi.org/10.3390/md16090306.
Full textAbstract:
This study investigated the anti-obesity effects of collagen peptide derived from skate skin on lipid metabolism in high-fat diet (HFD)-fed mice. All C57BL6/J male mice were fed a HFD with 60% kcal fat except for mice in the normal group which were fed a chow diet. The collagen-fed groups received collagen peptide (1050 Da) orally (100, 200, or 300 mg/kg body weight per day) by gavage, whereas the normal and control groups were given water (n = 9 per group). The body weight gain and visceral adipose tissue weight were lower in the collagen-fed groups than in the control group (p < 0.05). Plasma and hepatic lipid levels were significantly reduced by downregulating the hepatic protein expression levels for fatty acid synthesis (sterol regulatory element binding protein-1 (SREBP-1), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC)) and cholesterol synthesis (SREBP-2 and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR)) and upregulating those for β-oxidation (peroxisome proliferator-activated receptor alpha (PPAR-α) and carnitine palmitoyltransferase 1 (CPT1)) and synthesis of bile acid (cytochrome P450 family 7 subfamily A member 1 (CYP7A1)) (p < 0.05). In the collagen-fed groups, the hepatic protein expression level of phosphorylated 5′ adenosine monophosphate-activated protein kinase (p-AMPK) and plasma adiponectin levels were higher, and the leptin level was lower (p < 0.05). Histological analysis revealed that collagen treatment suppressed hepatic lipid accumulation and reduced the lipid droplet size in the adipose tissue. These effects were increased in a dose-dependent manner. The findings indicated that skate collagen peptide has anti-obesity effects through suppression of fat accumulation and regulation of lipid metabolism.
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Evans, R. D., M. Stubbs, G. F. Gibbons, and E. A. Newsholme. "The life and work of Dermot Hedley (‘Derek’) Williamson (1929–1998)." Biochemical Society Transactions 29, no. 2 (May 1, 2001): 237–40. http://dx.doi.org/10.1042/bst0290237.
Full textAbstract:
Derek Williamson's scientific career spanned the ‘Golden Age’ of research into metabolic regulation, to which he made an important and sustained contribution. Derek joined Hans Krebs' laboratory at Sheffield University in 1946 and moved to Krebs' MRC Unit in Oxford in 1960. He elaborated an enzymic method for the determination of acetoacetate and 3-hydroxybutyrate [Williamson, Mellanby and Krebs, Biochem. J. (1962) 82, 90–96], which opened up the field of ketone body metabolism and its regulation and became a Citation Classic. Another Citation Classic followed [Williamson, Lund and Krebs, Biochem. J. (1967) 103, 514–527]. He moved with Krebs to the Metabolic Research Laboratory at the Radcliffe Infirmary in 1967, where he blossomed, formulating his ideas about the integrated regulation of metabolic pathways, particularly with regard to fatty acid oxidation, lipid synthesis and ketone body metabolism. His success was illustrated by more than 200 publications. Derek implanted and nurtured a sense of the excitement of scientific discovery in his colleagues and students, and he worked hard to provide a friendly, supportive and encouraging environment. Many lives have been enriched by the privilege of working with him.
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OSMUNDSEN, Harald, Hélène BRAUD, Frédérick BEAUSEIGNEUR, Joseph GRESTI, Marcelline TSOKO, and Pierre CLOUET. "Effects of dietary treatment of rats with eicosapentaenoic acid or docosahexaenoic acid on hepatic lipid metabolism." Biochemical Journal 331, no. 1 (April 1, 1998): 153–60. http://dx.doi.org/10.1042/bj3310153.
Full textAbstract:
(1) Effects of dietary treatment of male albino rats with eicosapentaenoic acid (EPA) or docosahexaenoic acid on hepatic mitochondrial lipid metabolism have been investigated. (2) Mitochondria isolated from rats given these treatments were shown to have increased ability to respire on acyl-CoA esters in the presence of malonate. This effect was expressed with most of the long-chain acyl-CoA esters used as substrates. When malonate in the incubations was replaced with malate, mitochondria from treated animals were found to exhibit diminished rates of respiration on polyunsaturated acyl-CoA esters, in particular linolenoyl-, eicosapentaenoyl- and docosahexaenoyl-CoA. This phenomenon could not be attributed to changes in activity of carnitine palmitoyltransferase I or in peroxisomal β-oxidation. (3) Uncoupled respiration on glutamate, malate or succinate was also affected by treatment with EPA. With liver mitochondria isolated from rats that had been treated with a ω-3 fatty acid in the fasted state, the respiratory rates were lower than those observed with mitochondria isolated from control rats. Respiratory rates with mitochondria isolated from rats given the ω-3 fatty acid in the fed state was not significantly different from control rates. (4) In rats treated with EPA in the fed state, the amount of EPA incorporated into mitochondrial lipids was markedly more increased as compared to rats given ω-3 fatty acid in the fasted state. Incorporation of dietary EPA into tissue lipids was investigated, also following mildronate treatment of rats (an inhibitor of carnitine biosynthesis). (5) A hypolipidaemic effect of dietary EPA was only observed when the fatty acid was given to fed rats. Rats treated with EPA in the fasted state, in contrast, exhibited hypoglycaemia, the hypolipidaemic effects now being absent. (6) These results suggest that hypolipidaemia is most pronounced when the metabolic state favours incorporation of dietary EPA into body lipids rather than its β-oxidation, as mediated by the fed/fasted transition or by treatment with mildronate.